Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000806163 | SCV000946147 | uncertain significance | Bethlem myopathy 1A | 2020-02-14 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with serine at codon 321 of the COL6A2 protein (p.Pro321Ser). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and serine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with COL6A2-related disease. This variant is present in population databases (rs745678446, ExAC 0.04%). |
| Ambry Genetics | RCV004028238 | SCV004929530 | uncertain significance | Inborn genetic diseases | 2023-11-02 | criteria provided, single submitter | clinical testing | The c.961C>T (p.P321S) alteration is located in exon 10 (coding exon 9) of the COL6A2 gene. This alteration results from a C to T substitution at nucleotide position 961, causing the proline (P) at amino acid position 321 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |